tbuckley/cabot-search huggingface dataset:
A prospective clinical trial to evaluate the performance of a multi-analyte blood test for early detection of hepatocellular carcinoma among at-risk patients with liver cirrhosis: The CLiMB study.
Authors: Dhruvajyoti Roy, Jianfeng Xu, David J. Taggart, Max A. Gallant, Kisha Bush, Octavia Reed, Arshia Akhtar, Ju Dong Yang, Mindie Nguyen, Wei Li, Richard A. Van Etten
Journal: Journal of Clinical Oncology (2023)

TPS617 Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death in patients with cirrhosis in the U.S. HCC surveillance is associated with significant improvements in early tumor detection, receipt of curative therapy and overall survival in patients with cirrhosis. However, current surveillance strategies suffer from poor adherence and suboptimal sensitivity. The multi-analyte HelioLiver test is a novel blood test for the early detection of HCC. The test provides a qualitative result based on a multiparametric algorithm that incorporates information from cell-free DNA (cfDNA) methylation markers, protein tumor markers (AFP, AFP-L3%, DCP) and patient demographic characteristics (sex, and age). Here, we describe the protocol for a prospective, multicenter clinical trial designed to investigate the performance of this multi-analyte blood test in cirrhosis patients at risk for HCC. Methods: The Prospective Clinical Trial to Detect Liver Cancer through Quantification of cfDNA Methylation in Blood Samples (CLiMB) is a longitudinal, multicenter, prospective study with a targeted enrollment of 1,600 participants. The main inclusion and exclusion criteria are described in the table. Within the Initial Surveillance Visit (t=0 months), all enrolled subjects will provide blood specimens for the multi-analyte blood test and undergo conventional ultrasound to examine the liver. Every subject will then undergo diagnostic imaging by multiphasic MRI to determine the clinical truth. The results of diagnostic imaging will be scored by a Liver Reporting and Data System (LI-RADS) score and the number and size of any malignant lesions identified will be recorded. After the Initial Surveillance Visit (t=0 months), subjects with an indeterminant HCC finding by MRI (LI-RADS 3) will be recommended to have up to three Follow-Up Visits (t=6 months, t=12 months, and t=18 months) to attempt to resolve the clinical truth for these subjects. The primary endpoints of the trial are to demonstrate the superiority for sensitivity and non-inferiority for specificity of the multi-analyte blood test over ultrasound for the detection of HCC. The data of all diagnostic imaging by MRI will be saved and uploaded for evaluation by a blinded, centralized team of radiologists, which will be used as the basis of the clinical truth for all subjects. All participants are currently enrolled across the U.S. from over 40 clinical sites. Clinical trial information: NCT03694600 . [Table: see text]
A multicenter, case-control study of a novel multi-target fecal DNA test for colorectal cancer detection.
Authors: Jiaxi Peng, Meichen Yin, Ruijingfang Jiang, Zhilong Li, Duan Zhuo, Hongyue Qu, Mengxue Luo, Qian Liu, Weijia Jiang, Jianlong Sun, Jia Lin, Yuying Wang
Journal: Journal of Clinical Oncology (2023)

26 Background: Globally, colorectal cancer (CRC) is the fourth most frequently occurring cancer and is the second leading cause of cancer-related deaths. Early detection and diagnosis of pre-cancer lesions and CRCs at curable stages could prevent the disease or improve patient survival. Colonoscopy, the current gold-standard approach for CRC screening, is an invasive procedure, and novel non-invasive alternatives are needed. Methods: In present study, we developed a novel multi-target fecal DNA based assay, which integrates detection of two stool DNA (sDNA) methylation markers by quantitative methylation-specific PCR (qMSP) and immunochemical fecal occult blood test. We performed a multi-center case-control study to validate the diagnostic performance of this novel multi-target assay. Thus far, we collected stool specimens from a total of 784 subjects including CRC, advanced adenoma, nonadvanced neoplasms and individuals with negative findings on colonoscopy from six sites across China. All participants underwent colonoscopy; the stool specimens were tested with the multi-target fecal DNA test as well as a quantitative FIT test (OC FIT-CHEK, Eiken) in parallel in order to perform head-to-head comparison of the test performance of both assays. Results: The multi-target fecal DNA test demonstrated a higher sensitivity (96.1%) than FIT (85.3%) for CRCs (n=204). Meanwhile, 20 of 39 (51.3%) patients with advanced adenoma tested positive by the fecal DNA test, which was remarkably superior to FIT (7 of 39 tested positive, 17.9%). Among 541 participants with nonadvanced neoplasms or negative findings on colonoscopy, the specificity of the DNA test was 86.9%, compared with a specificity of 93.1% achieved by FIT. Within the control group, the DNA test and FIT yielded a specificity of 90.5% and 94.9% respectively for individuals with negative results on colonoscopy. Conclusions: The novel multi-target fecal DNA test exhibited notably superior sensitivity for both CRC and advanced adenoma cases than the commercially quantitative FIT test, while sacrificing some specificity. Our results suggest that this novel multi-target fecal based test may be used as an effective tool for early detection and pre-screening of CRC. Prospective study will be conducted to further evaluate the clinical performance and cost-effectiveness of this assay.
The effect of potassium-competitive acid blocker tegoprazan on gastric cancer cells.
Authors: Sang Kil Lee
Journal: Journal of Clinical Oncology (2023)

385 Background: Proton pump inhibitors (PPI) and potassium-competitive acid blocker (P-CAB) are both effective gastric acid secretion blockers. PPI was reported to inhibit proliferation and induce apoptosis of gastric cancer. However, no study on the effect of Tegoprazan, a novel P-CAB, on gastric cancer have been attempted. Methods: In this study, the anti-cancer effect of tegoprazan in gastric cancer cell line AGS and MKN74 were analyzed with esomeprazole (PPI) as a control. After treatment with tegoprazan and esomeprazole, AGS cells were analyzed with with RNA sequencing and Ingenuity Pathway Analysis (IPA). MTT assays, AnnexinV-FITC/PI staining, flow cytometry and western blot were used for subsequent analysis. The wound-healing assay, matrigel chamber assays, colony forming assay, and western blot of epithelial-mesenchymal transition (EMT) markers were used for analysis of oncogenic and migratory ability. Results: In RNA sequencing and subsequent IPA analysis, tegoprazan significantly increased the pathways involved in cell death of gastric cancer cell compared to esomeprazole. MTT assays proved that tegoprazan inhibits proliferation of AGS and MKN74 cells in dose-dependent manner. AnnexinV-FITC/PI staining and western blot demonstrated that tegoprazan stimulates apoptosis of gastric cancer cells. PI staining and flow cytometry confirmed that tegoprazan blocks G1/S phase entry, finally leading to cell cycle arrest. Moreover, wound-healing assay, matrigel chamber assays, colony forming assay, and western blot of epithelial-mesenchymal transition (EMT) markers indicated that tegoprazan inhibits cell migration, invasion, colony formation, and EMT. To determine key molecule of anti-cancer effect of tegoprazan, upstream regulator analysis in IPA was done and cMYC has strong effect on G1/S phase entry, through PI3K/AKT/GSK3β signaling pathway in this experiment. In this study, the experimental results for tegoprazan showed significant changes compared to esomeprazole. Conclusions: Our findings showed that tegoprazan has more evident anti-cancer effect than esomeprazole. cMYC could be a key molecule for anti-cancer effect through PI3K/AKT/GSK3β signaling pathway by tegoprazan in gastric cancer.
Short- and long-term real-world survival for metastatic bile duct cancer, 2000 to 2018.
Authors: Sarah Jeanne Wood, Van Nghiem, Grant Richard Williams, Ravi Kumar Paluri, Darryl Alan Outlaw, Olumide B. Gbolahan
Journal: Journal of Clinical Oncology (2023)

523 Background: Real-world survival outcomes in metastatic biliary tract cancer (BTC) are largely unknown. Quoted numbers are often based on reports of clinical trials and hospital registry data and may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of standard combination chemotherapy since 2010 on survival is unclear. We performed a population-based survival analysis of patients who presented with metastatic BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. Methods: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we collected data for patients diagnosed with metastatic BTC from 2000 to 2018 and stratified by overall survival (OS) of ≤ 3 months (short-term survivors) or ≥ 12 months (long-term survivors), before and after 2010. Additional patient and tumor characteristics, including anatomic location, prior surgical intervention, age, sex, race, and marital status were retrieved. Survival was analyzed using the Kaplan-Meier method. Multivariate cox regression models assessing effects of patient and tumor characteristics between short-term and long-term survivors were employed. Results: Of the 13,287 cases retrieved, 57% were female. Median age was 68 years (range 10-100). Prognosis correlated with anatomic location, marital status, and period of diagnosis. 41% of patients were short term survivors and only 20% were long term survivors. Median OS was 4.5 months for the entire cohort. Median OS only improved marginally from 3.5 months pre-2010 to 4.5 months post-2010 ( p&lt;0.001). Long-term survivors tended to be younger, with a median age at diagnosis of 64 years vs 72 years ( p&lt;0.001). Within the long-term survivor cohort, intrahepatic disease was significantly associated with improved outcomes (HR 0.81, 95% CI 0.73 – 0.90, p= 0.001). Conclusions: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials as a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.
Impact of malnutrition on postoperative outcomes of patients undergoing gastrectomy for gastric cancer: A nationwide analysis between 2012 and 2017.
Authors: Vatsala Katiyar, Ishaan Vohra, Harishankar Gopakumar, Vivek R. Sharma
Journal: Journal of Clinical Oncology (2023)

315 Background: Gastrectomy offers a curative treatment option for non-metastatic gastric cancers (GC). Unfortunately, cancer associated malnutrition is a common and potentially actionable problem in GC patients. In this nationwide study, we analyzed the impact of malnutrition on outcomes of patients undergoing gastrectomy for GC. Methods: The Nationwide inpatient Sample database (NIS) was used to identify patients who underwent gastrectomy for gastric cancer from 2012-2017 using ICD 9 and ICD 10 codes. The population was then divided into patients with or without PEM (Protein energy malnutrition) to compare their outcomes. Univariate and Multivariable logistic and linear regression models were used to analyze mortality and healthcare resource utilization. Results: Of the 6,620 patients identified, 4,607 (69.6%) patients were ≥ 60 years old and 3,972 (60%) were males. Majority were White (49.1%) followed by Asians (20.3%). 2,052 (31%) patients were malnourished. Patients with PEM had higher rates of sepsis [adjusted Odds ratio (aOR) 3.6(2.4-5.4), p =0.000], shock [aOR 2.9(1.9-4.5), p =0.000], acute kidney injury [aOR 2.1(1.5-2.9), P&lt;0.001], ICU admissions [ aOR 1.9(1.3-2.9), p =0.001], and higher post operative mortality [aOR 2.5 (1.5-4.3), p =0.001]. Mean Length of stay was longer in PEM patients as compared to non-PEM patients (16.2 vs 9.4 days). On survival analysis, overall survival (OS) was significantly worse for patients with PEM undergoing gastrectomy [HR adj: 1.14 (p=0.04)]. A comparison of these outcomes has been detailed in the table. Conclusions: In this analysis, we highlight the importance of nutrition for gastric cancer patients undergoing gastrectomy. Ensuring adequate nutritional status prior to surgery can improve patient outcomes and decrease health care costs.[Table: see text]
Efficacy of nivolumab and ipilimumab in patients with hepatocellular carcinoma with prior immune-checkpoint inhibitor treatment.
Authors: Jaekyung Cheon, Beodeul Kang, Sang-Hoon Jung, Chan Kim, Hongjae Chon
Journal: Journal of Clinical Oncology (2023)

554 Background: Nivolumab plus ipilimumab (NIVOIPI) demonstrated promising efficacy in patients with unresectable hepatocellular carcinoma(uHCC) in the phase 1/2 CheckMate 040 trial. However, as atezolizumab plus bevacizumab (Ate/Bev) is a new first-line standard systemic therapy, it is necessary to evaluate the role of NIVOIPI after treatment with Ate/Bev. Methods: Patients with uHCC who received NIVOIPI after previous systemic treatment were included. Patients received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks (four doses), followed by nivolumab (240 mg) every 2 weeks. Patients with Child B/C class and BCLC D stage uHCC were excluded. Patients who had at least one follow-up visit after the start of NIVOIPI were included. Results: A total of 47 patients were included with characteristics as follows: median age of 60 years (range, 37–79); hepatitis B (n = 40, 85.1%), hepatitis C (n = 2, 4.3%), non-viral (n = 5, 10.5%); BCLC B/C (n = 2, 4.3%; n = 45, 95.7%); macrovascular invasion (n = 12, 25.5%); extrahepatic metastasis (n = 41, 87.2%); and AFP ≥ 400 ng/ml (n = 26, 55.3%). Thirty-five (74.5%) patients had a history of prior immune-checkpoint inhibitor (ICI) treatment (n = 35, 74.5%), including Ate/Bev (n = 23, 48.9%). According to the RECIST 1.1, 12 patients achieved a partial response, resulting in an overall response rate (ORR) of 25.5% and disease control rate (DCR) of 42.6%. The ORR and DCR were 41.7% and 58.4% in ICI-naïve patients and 20.0% and 37.1% in patients with prior ICI treatment. The median follow-up duration was 5.7 months (95% confidence interval [CI], 5.4–6.1), the median progression-free survival was 1.4 months (95% CI, 1.1–1.7) in all patients, 1.3 months (95% CI, 0.1–1.1) in prior ICI-treated patients and was not reached in ICI-naïve patients. The median overall survival was not reached. The most common grade 3–4 toxicities were aspartate aminotransferase elevation (n = 4, 8.5%), neutropenia (n = 4, 8.5%), skin toxicity (n = 3, 6.4%), alanine transaminase elevation (n = 2, 4.3%) and pneumonitis (n = 2, 4.3%). There was one treatment-related death due to toxic epidermal necrolysis. Conclusions: NIVOIPI demonstrated clinical meaningful efficacy in patients with uHCC, with and without prior ICI treatment.
Chemotherapy-induced neuropathy in esophagogastric cancer.
Authors: Merel van Velzen, Marieke Pape, Jessy Joy van Kleef, Marije Slingerland, Laurens V. Beerepoot, Bianca Mostert, Nadia Haj Mohammad, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2023)

309 Background: Treatment of locally advanced and metastatic esophagogastric cancer (EGC) largely depends on systemic treatment including taxanes or platinum compounds – agents which are known to cause chemotherapy induced peripheral neuropathy (CIPN). To date, the extend of CIPN in EGC has not been investigated in real-world data. Methods: We identified patients with EGC from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort study of Oesophageal-gastric cancer Patients (POCOP) who underwent systemic treatment between 2016 and 2018 and completed at least one EORTC QLQ-CIPN20 questionnaire. Total CIPN scores and scores for the motor, sensory and autonomic scales (ranged 0-100) were calculated, and analyzed over time for patients receiving chemoradiation (CRT), peri-operative chemotherapy (POC) and patients primarily treated with palliative chemotherapy (PC). To gain insight in the differences between CIPN score at baseline and after 3, 6, 9, 12, 18 and 24 months we constructed linear mixed effect models. Results: We included 1052 EGC patients. 769 patients received CRT (response: 76% at baseline, 30% after 24 months), 143 received POC (response: 79% at baseline, 33% after 24 months) and 140 received PC (response: 74% at baseline, 28% after 12 months). Over time, neuropathy scores increased in all scales for patients receiving POC and PC, with a maximum increase of 16.5 points in total CIPN score after 6 months in the PC group compared to baseline. For patients receiving CRT, increase in neuropathy scores was more subtle, with a maximum increase in total CIPN score of 4.3 points after 24 months compared to baseline. Results of mixed effect models showed a significant increase of CIPN scores over time in all three groups compared to baseline, persisting for as long as two years after start of initial treatment. Conclusions: CIPN frequently occurs in EGC patients treated with chemotherapy, especially with PC. Due to the possible irreversibility of CIPN, it is important that clinicians inquire patients about neurotoxicity often, adjust the dose of neurotoxic agents as needed and that more research is done into strategies possibly preventing the occurrence of CIPN. Results of mixed model analysis to assess changes in total CIPN score over time. Each model was adjusted for age, sex, performance status and number of comorbidities. The model for POC and PC was also adjusted for use of oxaliplatin.[Table: see text] *p-value &lt;0.001 a Chemoradiotherapy b Peri-operative chemotherapy c Palliative chemotherapy, no estimates were calculated for 18 and 24 months due to the low number of responses.
Multisite institutional study of efficacy and safety of cabozantinib following immunotherapy in patients with advanced hepatocellular carcinoma.
Authors: Mathias Earl Palmer, Michael H. Storandt, Jennifer Gile, Tyler J. Zemla, Tanios S. Bekaii-Saab, Zhaohui Jin, Nguyen H. Tran, Amit Mahipal
Journal: Journal of Clinical Oncology (2023)

559 Background: Cabozantinib, a multikanase inhibitor, is approved by the Food and Drug Administration (FDA) for treatment of advanced stage hepatocellular carcinoma (HCC) following progression on sorafenib. The CELESTIAL study which demonstrated benefit from cabozantinib following sorafenib included only patients with Child Pugh class A liver function. Recently, bevacizumab plus atezolizumab has replaced sorafenib as the first line treatment for HCC. It is unclear whether there is benefit from using Cabozantinib following progression on immunotherapy as CELESTIAL trial included very few patients who received prior immunotherapy. We describe the outcomes of individuals with advanced stage HCC treated with Cabozantinib following progression on immunotherapy. Methods: This was a multicenter, retrospective analysis of patients with advanced HCC diagnosed between 2010-2021 at Mayo Clinic Arizona, Florida, and Minnesota. Progression free survival (PFS) and median overall survival analysis were performed using Kaplan-Meier method. Results: We identified a total of 26 patients with advanced stage HCC who received cabozantinib following progression on immunotherapy. The median age of patients was 61 years (range, 39 – 81) and the majority were male (85%). Eighteen (72%) patients had Child Pugh A at initiation of cabozantinib therapy. Four (15%) patients received cabozantinib as second line therapy, the rest received it as third line or later. PFS on cabozantinib was 2.1 months (95% CI: 1.3 – 3.9) and median overall survival from time of cabozantinib initiation was 7.7 months (95% CI: 5.3 – 14.9). PFS was shorter with Child Pugh Class B, 1.3 months (95% CI: 0.9 – NE) compared to those with Child Pugh Class A, 2.1 months (95% CI: 1.5 – 4); although this difference was not significant (p=0.55). Common adverse events included fatigue (50%), anorexia (35%), aspartate aminotransferase (AST) elevation (35%), and diarrhea (31%); 7 (26%) patients experienced Grade 3 or greater adverse events including hypertension, diarrhea, anorexia, and bowel obstruction. Two patients discontinued cabozantinib due to side effects including one for uncontrolled blood pressure elevations and the other due to fatigue. Conclusions: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy is unknown. Treatment with cabozantinib may improve clinical outcomes following progression on immunotherapy with similar adverse event profile. This study included patients with Child Pugh class B liver disease (28%) and heavily pretreated population and demonstrated mPFS and mOS similar to other work examining outcomes of cabozantinib in real world setting after progression on sorafenib. Further studies to determine optimal treatment sequencing for this patient population are needed.
Quality-of-life outcomes after total neoadjuvant short course radiotherapy, chemo-immunotherapy, and total mesorectal excision for locally advanced rectal cancer.
Authors: Ali Shamseddine, Laudy Chehade, Joseph Gergi Kattan, Sally Naji Temraz, Rula Amarin, Tala Awabdeh, Maya Charafeddine, Monita Al Darazi, Rim Turfa
Journal: Journal of Clinical Oncology (2023)

63 Background: A growing body of evidence supports total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC), however the optimal regimen is yet to be determined and little is known on the quality-of-life (QOL) implications of these therapies. We report QOL data from the Averectal study, which assessed the efficacy and safety of neoadjuvant short course radiotherapy (SCR) plus chemo-immunotherapy for patients with LARC. Methods: Between July 2018 and October 2020, patients enrolled in the Averectal study were invited to fill the Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C) throughout their treatment. We analyzed results at baseline (T0), at completion of SCR and chemo-immunotherapy (T1), and at last-follow up after total mesorectal excision (TME) (T2). Paired sample t-test was used to compare mean scores for individual patients. Results: 39 patients completed the FACT-C form at the specified points. Median follow-up duration was 25.7 months. Median age was 58 years (range 31-74 years), 25 (64.1%) were males, 1 (3.1%) had stage II disease and the rest (96.9%) had stage III. All patients received SCR then 6 cycles of mFOLFOX-6 plus avelumab followed by TME. The mean score differences of the FACT-C subscales at different time-points are summarized. At the end of TNT, the social (SWB), emotional (EWB), functional well-being (FWB) and colorectal cancer subscale (CCS) scores improved compared to baseline (not significant) but physical well-being score (PWB) worsened (21.05 vs 22.94 p=0.025). After TME, all scores except EWB and FWB improved compared to T1, and all scores improved compared to baseline. The CCS, which assesses colorectal cancer specific concerns, significantly improved between T0 and T2 (19 vs 21.06, p=0.003). Overall, trial outcome index (TOI), reflecting functional status, improved after TME compared to baseline. Conclusions: Adopting neoadjuvant chemo-immuno-radiotherapy followed by TME for LARC does not result in QOL deterioration compared to baseline, and can improve colorectal cancer specific concerns. Clinical trial information: NCT03503630 . [Table: see text]